Cyclodextrin-covered gold nanoparticles for targeted delivery of an anti-cancer drug
Cyclodextrin-covered gold nanoparticles for targeted delivery of an anti-cancer drug
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DOI：
10.1039/b816209c
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发表时间：
2009-01-01
影响因子：
--
通讯作者：
Kim, Chulhee
中科院分区：
文献类型：
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作者：
Park, Chiyoung;Youn, Hyewon;Kim, Chulhee
我们报告了一种新型的环糊精覆盖的金纳米颗粒（AuNP）载体的治疗能力，用于非共价包封抗癌药物。金纳米颗粒的表面功能化与环糊精作为药物口袋，抗表皮生长因子受体（抗EGFR）抗体作为靶向部分，和聚（乙二醇）（PEG）作为防污壳。将抗癌药物拉帕酮（b-Lapachone）有效地包封在金纳米粒子载体（AuNP-1）表面的环糊精疏水空腔中。通过使用MCF-7（低谷胱甘肽浓度）和A549细胞（高谷胱甘肽浓度）的实验证明了谷胱甘肽介导的b-拉帕醌从AuNP-1表面的释放。我们还表明，与不含靶向配体的AuNP-1相比，将抗EGFR抗体引入到AuNP载体（AuNP-2）上增加了AuNP载体的细胞内摄取。在体外细胞毒性研究中，AuNP-2与b-拉帕醌表现出比AuNP-1与b-拉帕醌引起的更高的凋亡作用。这项工作表明，覆盖有环糊精和肿瘤靶向配体的金纳米颗粒可能会在开发具有治疗和诊断模式的纳米颗粒方面找到有用的应用。
We report on the therapeutic ability of a novel cyclodextrin-covered gold nanoparticle (AuNP) carrier for noncovalent encapsulation of an anti-cancer drug. The surface of the AuNPs was functionalized with cyclodextrin as a drug pocket, anti-epidermal growth factor receptor (anti-EGFR) antibody as a targeting moiety, and poly(ethyleneglycol) (PEG) as an anti-fouling shell. b-Lapachone, an anticancer drug, was efficiently encapsulated into the hydrophobic cavity of cyclodextrin on the surface of the AuNP carriers (AuNP-1). The glutathione-mediated release of b-lapachone from the surface of AuNP-1 was demonstrated by an experiment with MCF-7 (low glutathione concentration) and A549 cells (high glutathione concentration). We also show that the introduction of an anti-EGFR antibody onto the AuNP carriers (AuNP-2) increased the intracellular uptake of AuNP carriers as compared with AuNP-1, which does not contain a targeting ligand. In the in vitro cytotoxicity study, AuNP-2 with b-lapachone exhibited a higher apoptosis effect than that caused by AuNP-1 with b-lapachone. This work suggests that AuNPs covered with cyclodextrin and tumor-targeting ligands may find useful applications for the development of nanoparticles with therapeutic and diagnostic modalities.